The object of the proposed investigation is to test the following two hypotheses concerning the differentiation of lymphocytes under the influences of the thymus; 1, Precursors of thymocytes and T lymphocytes (PT) residing in bone marrow can be identified by the presence of a specific cell surface antigen. Depletion of PT cells as well as T lymphocytes, from donor bone marrow inocula will result in depletion of graft-versus-host activity following bone marrow transplantion into histo-incompatible recipients and a reduction in the ability of bone marrow cells to restore T cell function in immuno-depressed histocompatible hosts. Maturation of thymocytes within the thymus is regulated by the levels of recirculating T lymphocytes in the peripheral lymphoid tissues. Depletion of recirculating cells by agents such as anti-lymphocyte serum, results in an increased rate of maturation of cells within the thymus. 2. Lymphocytes under the influence of the thymus differentiate into functionally different sub-population of peripheral T lymphocytes. One sub-population of short-lived, non- recirculating T lymphocytes functions as a source of precursors of cytotoxic and graft-versus-host effector cells. A second population of long-lived recirculating T lymphocytes amplifies both cell mediated and humoral immune responses. Cell mediated and humoral immune responses in the face of tumors and transplanted tissue may be increased or decreased by appropriate changes in the ratio between these T cell sub- populations. In order to test this hypothesis, well-characterized populations of recirculating and non-recirculating T lymphocytes, purified by various techniques, will be tested for their ability to interact in the in vitro and in vivo production of cell mediated and antibody-mediated immune responses.